- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Rima, X. Y., Majumder, S., Hu, C., Patel, D. S., Li, H., Huang, X., Nguyen, K. T., Doon-Ralls, J., Nagaraj, C. K., Hade, M. D., Magana, S. M., Shankar, E., Zhang, X., Stover, D. G., Ramaswamy, B., Reategui, E.Invasive lobular carcinoma (ILC) accounts for 10-15% of breast cancers. Despite favorable responses to anti-estrogen therapy, the dissemination of cancer cells and resistance to therapies are significant risks for patients with ILC. Late recurrences are prevalent in ILC, suggesting that disseminated tumor cell dormancy may be a mechanism preceding their late overt growth into metastatic lesions. Herein, we investigated the relationship between anti-estrogen resistance and dormancy through multidimensional in vitro models. The bioengineered platforms recapitulated the morphological characteristics of ILC […]
- by Lebraud, E., Aubert, O., Aouni, L., Garcia, V., Morin, L., Eloudzeri, M., Larmarthee, B., Zuber, J., Ramauge Parra, C., Try, M., Coemans, M., Abderrahmane, A., Taupin, J.-L., Jager, C., Holleville, Q., Normand, C., garcelon, N., Terzi, F., Rabant, M., Anglicheau, D.Introduction: Antibody mediated rejection (AMR) remains a leading cause of kidney allograft failure, with both HLA and non HLA antibodies implicated in its pathogenesis. The contribution of non HLA antibodies (non HLA Abs) to microvascular inflammation (MVI) and graft outcome, particularly in cases lacking donor-specific anti HLA antibodies (HLA DSAs), remains incompletely understood. Methods: We analyzed 571 post-transplant serum samples from 326 patients with histological features of AMR (AMRh) and 164 stable controls. Non HLA Abs were detected using the […]
- by Elsener, T. A., Cehovin, A., Yee, W.-X., Forrow, A., Palmer, S., Tang, C. M.Horizontal gene transfer (HGT) in bacteria is shaped by restriction modification systems (RMSs) that define genetic barriers between species and lineages. Neisseria gonorrhoeae harbours numerous RMS, most of which are part of its core genome. Here, we show that phase variation in these RMSs can limit interspecies and intraspecies plasmid exchange. While NlaIV likely influenced the acquisition of pConj from the meningococcus, phase variation of the NgoAV RMS produces epigenetically heterogeneous populations that present variable bottlenecks to within-species plasmid transmission, […]
- by Lammens, I., Declercq, J., Brown, A. S., Smole, U., Deswarte, K., Hoste, E., Herreman, K., Sang-aram, C., Browaeys, R., Baptista, A. P., Seurinck, R., Saeys, Y., Gevaert, P., Hammad, H., Lambrecht, B. N., Vanhee, S.Secondary lymphoid organs (SLO) are prototypic sites of antibody production, yet mucosal sites also generate and maintain mucosal antibodies during continued inflammation. Using a murine model of house dust mite induced airway inflammation, we show that prolonged allergen exposure induces tertiary lymphoid organs (TLO) within para-bronchial adventitial cuffs. Within these regions, IL1 signaling instructs fibroblasts to form niches that recruit, retain, and sustain lung antibody-secreting cells (ASCs) through chemokine induction. These mucosal ASCs share immunoglobulin repertoires with TLO derived germinal […]
- by Flores, I. S., Nguyen, V. T., Bae, J. S., Urlaub, A., Gellner, R., Kading, R. C., Romero-Weaver, A. L., Simubali, L., Saili, K., Simulundu, E., Reeves, L. E., Lee, Y.The biodiversity of mosquito taxa beyond Anopheles malaria vectors has been understudied in many parts of Africa. Here, we provide a new species record of mosquitoes from Macha and its surrounding locations in southern Zambia, as well as an updated list of species from the region. With the addition of 19 new species records in this region, the total list of mosquito species reported in Macha is now 46. We present high-resolution focus-stacked photographs of some of these species, many […]
- by Arango, B. G., Selleghin-Veiga, G., Moreno-Santillan, D. D., Ensminger, D. C., Vazquez, J. M., Tarvin, R., Nery, M., Godard-Codding, C., Vazquez-Medina, J. P.Hypoxia-inducible factors (HIFs) are transcriptional regulators that orchestrate the canonical response to low-oxygen tension in animal cells. Vertebrates possess three HIF-a isoforms, which arose from two gene duplication events of the ancestral HIF-1a gene. Here, we examined whether the HIF gene family (HIF-1a, HIF-2a, HIF-3a, and HIF-1aN inhibitor) shows evidence of positive selection in hypoxia-tolerant reptiles (Testudines), compared evolutionary patterns within the family, and assessed the transcriptional response to hypoxia in primary cells derived from a hypoxia-tolerant (Caretta caretta) and […]
- by Lagune, M., Bianchi, N., Herren, M., Prados, J., Caillon, A., Kulkarni, G., Silva, F., Von Rohr, O., Sierra, R., Colpaert, M., Gentry, M., Veening, J.-w., Kloehn, J., Schmolke, M., Becattini, S.Bacterial pneumonia remains a major cause of morbidity and mortality following influenza A virus (IAV) infection. However, the adaptive mechanisms that enable pathogen expansion in the post-viral lung remain poorly defined. Here, using a mouse model of IAV-Streptococcus pneumoniae superinfection, we characterize bacterial transcriptional reprogramming in vivo. We identify alcohol dehydrogenases (AdhA and AdhE), that support NAD+ regeneration during mixed-acid fermentation, as key determinants of bacterial fitness specifically in the IAV-primed lung. Genetic deletion of these results in a pronounced […]
- by Mugglestone, S., Ganis, G., Hughes, S.High-frequency stimulation (HFS) is a human surrogate model of secondary hyperalgesia and a key experimental tool for understanding the mechanisms and modulation of central nociceptive pathways. An emerging area of research focuses on the role of top-down endogenous analgesic systems during secondary hyperalgesia development. However, the test-retest reliability of the early temporal changes in sensitivity are poorly understood. In the present study, we investigated the between-session reliability of the early temporal dynamics and late-phase expression of HFS-induced changes in mechanical […]
- by Silva, B., Tsakani, E., De, J., Kontopoulos, A., Gaspar, P., Hiridjee, A., Rosselli, C., de Juan-Sanz, J., Campusano, J. M., Treiber, C. D., Waddell, S., Miguel-Aliaga, I., Hadjieconomou, D.Animals must align intestinal plasticity and feeding with reproductive state, yet the checkpoint that gates these adaptations is unknown. Here we show that an ovary-to-enteric-neuron axis gates the onset of maternal gut plasticity in Drosophila. Genetic sex establishes endocrine competence in a subset of enteric neurons via the sex determination pathway, enabling female-specific expression of the relaxin-family receptor Lgr3. After mating, steroid signalling increases Lgr3 receptor expression, priming these neurons for reproductive adaptation. Once oocytes mature fully, follicle cells secrete […]
- by Shahbabaie, A., Abdelmotaleb, M., Kocatas, H., Niemann, F., Antonenko, D., Floeel, A., Meinzer, M.Background: Neural network effects of transcranial direct current stimulation (tDCS) are poorly understood. Here, we introduce an empirically informed, multimodal functional magnetic resonance imaging (fMRI) based framework suited for guiding stimulation target selection and hypothesis-based data analysis in focal tDCS-fMRI studies. Methods: We illustrate our approach using data of 37 healthy individuals (19 females; mean +/- SD age = 25.8 +/- 5.9) recruited from a multicenter tDCS-fMRI study (www.memoslap.de/en/home/). Participants completed resting-state (RS- and task-fMRI (object-location memory, OLM, or associative […]
- by Karjalainen, S., Leukkunen, J., Kullberg, T., Parviainen, T.A central challenge in supporting learning and designing learning environments is to understand individual differences in learning experiences. However, despite growing interest in examining learning experiences in naturalistic contexts, studies employing multimethod and hyperscanning approaches remain scarce. In this study, electroencephalography (EEG) and electrocardiography (ECG) were combined to measure brain activity, heart rate, and heart rate variability simultaneously during authentic learning situations in aviation and forestry. We investigated how students and instructors cardiac and brain activity varied across different phases […]
- by Waters, R. C., Gore, I. R., Brown, C. J., Skweres-Gilmartin, A. L., Rathaur, A. B., Gould, E.Early-life adversity has a lasting negative impact on social behavior in both humans and rodents. Sex differences exist in functional outcomes of postnatal stress, but underlying mechanisms remain incompletely explored. Using the limited bedding and nesting paradigm, a mouse model of developmental scarcity, we found sex differences in social behavior with adult males showing impaired social recognition and adult females showing intact social recognition with enhanced social novelty preference. Perineuronal nets, specialized extracellular matrix structures, are known to inhibit developmental […]
- by Woods, D. P., Adams, G., Mozumder, R., Dang, W., Chen, A. Y., Constantinidis, C., Gonzales, D. L.Neurophysiological recordings from non-human primates (NHPs) have traditionally relied on rigid microelectrode arrays made from stainless steel or silicon. While these devices enable high-quality recordings, a fundamental mechanical mismatch between rigid materials and soft brain tissue leads to inflammation, gliosis, and signal instability. In particular, brain micromotion causes continuous drifting of neurons relative to fixed electrodes, compromising single-unit tracking during both chronic and acute recordings. Flexible, penetrating electrodes offer a promising solution, but their adoption in NHPs has been hindered […]
- by Tian, L., Gottschalk, S.Immunotherapy represents a promising strategy to improve outcomes in pediatric leukemia; however, its efficacy remains considerably lower in acute myeloid leukemia (AML) compared with B-cell acute lymphoblastic leukemia (B-ALL). To characterize T-cell subsets in AML and B-ALL at diagnosis, we took advantage of existing data sets and performed an integrated single-cell RNA sequencing (scRNA-seq) analysis of T cells present in the bone marrow of pediatric patients with B-ALL (n=89) and AML (n=26), and healthy donors (n=9). In total, 47,610 T […]
- by Viet, J., Duot, M., Mereau, A., Audic, Y., Jan, I., Reboutier, D., Le Goff – Gaillard, C., Coomson, S. Y., Lachke, S. A., Gautier-Courteille, C., Paillard, L.Precise post-transcriptional regulation of gene expression is essential for vertebrate lens development. Disruption of the gene encoding the RNA-binding protein CELF1 leads to early-onset cataract in mice. Here, using iCLIP-seq in lenses, we mapped transcriptome-wide CELF1 binding sites, revealing interactions with the 3'UTRs of key transcripts involved in lens development and pathology like Gja8, Jag1, Maf, Pax6, or Prox1. Integrated analysis with transcriptomic data and luciferase reporter assays demonstrated that binding of CELF1 protein represses its target mRNAs by destabilizing […]
- by Thorseth, M.-L., Johansen, A. Z., Baker, K. J., Carretta, M., Roemer, A. M. A., Jensen, C., Jurgensen, H. J., Linder, H., Czajkowski, N. K., Kuczek, D. E., Fjaestad, K. Y., Engelholm, L. H., Willumsen, N., Kim, K., Andersen, M. H., Groentved, L., Madsen, D. H.Solid tumors are often characterized by a dense extracellular matrix (ECM) that contributes to increased tissue stiffness. Collagen type I is the main component of the ECM and its abundance in tumors is frequently associated with poor prognosis. In vitro studies suggest that a high collagen density promotes tumor invasion and modulates immune responses. However, recent in vivo findings have questioned the pro-tumorigenic role of collagen type I. In this study, we investigate the role of collagen for pancreatic tumor […]
- by Oros Rodrigo, S., Fu, J., Greiner, J., Madl, J., Linder, M., Zgierski-Johnston, C., Loewe, A., Kohl, P., Rog-Zielinska, E.The transverse-axial tubular system (TATS) enables close structural and functional coupling between plasma membrane and sarcoplasmic reticulum of cardiomyocytes. It supports fast and efficient Ca2+-induced Ca2+ release upon cell depolarisation, crucial for excitation-contraction coupling in the heart. Due to the small diameter and tortuosity of individual tubules, the TATS forms a domain of restricted diffusive transport. It has previously been suggested that, as a consequence of an uneven distribution of Ca2+ influx and efflux pathways in TATS compared to outer […]
- by Joffe, A. M., Chorlay, A., Huzar, J., Hasnain, J., Geissler, P. L., Fletcher, D. A.Macrophages recognize and phagocytose opsonized target cells, including those coated with IgG antibodies. This process relies on binding of IgG to Fc{gamma} receptors (Fc{gamma}R) expressed on the macrophage surface, resulting in formation of a phagocytic synapse. Since the surface of both macrophages and target cells are densely packed with macromolecules of diverse sizes, most of which are not directly involved in phagocytic signaling, it is possible for tall 'bystander' proteins to sterically interfere with Fc{gamma}R engagement. Here, we use cell-like […]
- by Narrissamprakash, H., Haccard, O., Li, Z., Pollet, N., Marheineke, K.DNA replication in multicellular organisms follows a tightly regulated spatio-temporal program. Although the mechanisms underlying this replication program remain only partially understood, studies in model systems such as Xenopus laevis have highlighted the importance of titrating low-abundance replication factors. Whole-genome duplications as a consequence of polyploidization introduce additional layers of complexity, yet comparative analyses of replication programs across closely related polyploid species are scarce. Here, we developed an interspecies in vitro replication system using X. laevis egg extracts and sperm […]
- by Vargas Urdaneta, C. D., Barros, M. T.Extrusion bioprinting is moving from proof-of-concept demonstrations toward repeatable, manufacturing-style workflows, but the nozzle remains a persistent bottleneck. Inside compact, opaque channels, bioinks experience strong geometric forcing that sets the local shear environment for cells, the pressure demand on the printer, and the uniformity of deposition. Multi-outlet nozzles are attractive because they promise higher throughput by splitting one feed into parallel filaments, yet in practice they often suffer from uneven outlet delivery and junction-driven shear hotspots. As a result, nozzle […]